Serotonin is a brain chemical that carries signals across the synapse, or gap between nerve cells. The supply of serotonin is regulated by the serotonin transporter (SERT). In 2005, a team of Vanderbilt researchers led by Randy Blakely and James Sutcliffe identified rare genetic variations in children with ASD that disrupt SERT function.
In a new study published this week in the Proceedings of the National Academy of Sciences (PNAS), the researchers report the creation of a mouse model that expressed the most common of these variations.
The change is a very small one in biochemical terms, yet it appears to cause SERT in the brain to go into "overdrive" and restrict the availability of serotonin at synapses.
"The SERT protein in the brain of our mice appears to exhibit the exaggerated function and lack of regulation we saw using cell models," said Blakely, director of the Vanderbilt Silvio O. Conte Center for Neuroscience Research.
"Remarkably, these mice show changes in social behavior and communication from early life that may parallel aspects of ASD," noted first author Jeremy Veenstra-VanderWeele, assistant professor of Psychiatry, Pediatrics and Pharmacology.
The researchers conclude that a lack of serotonin during development may lead to long-standing changes in the way the brain is "wired."
In 1961, investigators at Yale discovered that as many as 30 percent of children with autism have elevated blood levels of serotonin, a finding described as "hyperserotonemia."
Since then, these findings have been replicated many times. Indeed, hyperserotonemia is the most consistently reported biochemical finding in autism, and is a highly inherited trait. Yet, the cause or significance of this "bio-marker" has remained shrouded in mystery.
Until now. In the current study, Veenstra-VanderWeele, Blakely and their colleagues showed that they could produce hyperserotonemia in mice that express a variant of a human SERT gene associated with autism.
Because the genetic change makes the transporter more active, higher levels of serotonin accumulate in platelets and therefore in the bloodstream. In the brain, overactive transporters should have the opposite effect – lowering serotonin levels at the synapse and producing behavioral changes relevant to autism. That's exactly what the researchers observed.
Of course, no mouse model can completely explain or reproduce the human condition. Neither does a single genetic variation cause autism. Experts believe the wide spectrum of autistic behaviors represents a complex web of interactions between many genes and environmental factors.
But animal models are critical to exploring more deeply the basis for the developmental changes that are observed in ASD. The scientists are using these mice to explore how altered brain serotonin levels during development may produce long-lasting changes in behavior and impact the risk for autism.
Scientists from the National Institute of Mental Health, the Medical University of South Carolina and the University of Texas Health Science Center in San Antonio contributed to the study.
The research was supported by the National Institutes of Health, the advocacy organization Autism Speaks and the American Academy of Child and Adolescent Psychiatry.
Bill Snyder | EurekAlert!
Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering